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Azathioprine in orbital apex syndrome

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Saptagirish Rambhatla
Saptagirish Rambhatla
Saptagirish Rambhatla
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Neha Arora at ASG Eye Hospital
Neha Arora
  • ASG Eye Hospital
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Abstract

Orbital Apex Syndrome (OAS) is commonly caused by specific inflammations, infections, neoplasms, iatrogenic, trauma, vascular and non-specific orbital inflammation (NSOI). OAS secondary to NSOI responds rapidly to corticosteroids. There are very few case reports on azathioprine as additional treatment modality in OAS secondary to NSOI. We are presenting a 42 years old female who had recurrent episodes of painful ophthalmoplegia, treated with steroid therapy. Patient was steroid dependant. Therefore, she was started on azathioprine 2-3mg/kg body weight for 36 weeks. She had complete remission of the painful ophthalmoplegia, with no further recurrence on 6 months follow-up.
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Indian Journal of Pharmacy and Pharmacology 2020;7(3):210–212
Content available at: https://www.ipinnovative.com/open-access-journals
Indian Journal of Pharmacy and Pharmacology
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Case Report
Azathioprine in orbital apex syndrome
Neha Arora1, Saptagirish Rambhatla1,*
1Dept. of Orbit and Oculoplasty, Sankara Eye Hospital, Bangalore, Karnataka, India
ARTICLE INFO
Article history:
Received 13-09-2020
Accepted 25-09-2020
Available online 23-10-2020
Keywords:
Orbital apex Syndrome
Non specific orbital inflammation
Azathioprine
ABSTRACT
Orbital Apex Syndrome (OAS) is commonly caused by specific inflammations, infections, neoplasms,
iatrogenic, trauma, vascular and non-specific orbital inflammation (NSOI). OAS secondary to NSOI
responds rapidly to corticosteroids. There are very few case reports on azathioprine as additional treatment
modality in OAS secondary to NSOI. We are presenting a 42 years old female who had recurrent episodes
of painful ophthalmoplegia, treated with steroid therapy. Patient was steroid dependant. Therefore, she was
started on azathioprine 2-3mg/kg body weight for 36 weeks. She had complete remission of the painful
ophthalmoplegia, with no further recurrence on 6 months follow-up.
© 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC license
(https://creativecommons.org/licenses/by-nc/4.0/)
1. Introduction
Orbital apex syndrome (OAS) is described as a syndrome
involving damage to oculomotor, trochlear, abducens
and ophthalmic branch of the trigeminal nerves (V1)
in association with optic nerve dysfunction. Based on
anatomical location, two other syndromes that can have
overlapping features are the superior orbital fissure
syndrome/ Rochon-Duvigneaud syndrome and Tolosa Hunt
Syndrome (THS).
The common causes of OAS are specific inflammations,
infections, neoplasms, iatrogenic, trauma, vascular and non-
specific orbital inflammation (NSOI).
We hereby present azathioprine as a treatment option in
OAS secondary to NSOI.
2. Case Report
A 42 years old female presented with complaints of
binocular diplopia of 2 days duration, with no history of any
systemic illness. Examination revealed 150left exotropia
and hypertropia with head tilt towards right side. Best
corrected visual acuity (BCVA) was 6/6 in both the eyes and
colour vision was normal.
* Corresponding author.
E-mail address:saptagirishr@gmail.com (S. Rambhatla).
Over a period of next 3 days, visual acuity reduced
to 6/9 with ptosis in the left eye and painful limitation
of all extraocular movements (EOM), corneal sensations
were normal. There was no relative afferent pupillary defect
(RAPD) and fundus was normal in both eyes. Patient was
diagnosed with left side OAS secondary to NSOI. MRI
was within normal limits with clear para nasal sinuses
and normal orbital apex (Figures 1 and 2). Patient was
given intravenous dexamethasone 8mg and 60 mg/day of
oral prednisolone for a week. She got relieved of pain
immediately after the steroid infusion.
Over the next 2 days, in spite of oral steroids, visual
acuity reduced to 6/12p with limitation of all EOM
associated with pain, there was increase in ptosis and
no RAPD with normal fundus examination. Patient was
started on intravenous methylprednisolone 500mg for 3
consecutive days with good response to the medication.
She developed mild pain 2 weeks later. Intravenous
methylprednisolone 500mg was repeated again along with
oral prednisolone at 1mg/kg tapered over 9 weeks.
Patient reported pain in the left eye as the dosage of
oral steroids reached 20 mg per day. She was started on
oral azathioprine 50 mg twice a day along with 30mg oral
prednisolone tapered over 3 weeks. Oral azathioprine was
increased to 50mg three times a day with monthly complete
https://doi.org/10.18231/j.ijpp.2020.034
2393-9079/© 2020 Innovative Publication, All rights reserved. 210
Arora and Rambhatla / Indian Journal of Pharmacy and Pharmacology 2020;7(3):210–212 211
Fig. 1:
Fig. 2:
blood counts, liver and renal function tests and serum C-
reactive protein assay. Patient showed good response to
medication with no diplopia or pain.
Oral Azathioprine was continued at a dose of 50mg thrice
daily for a period of 5 weeks. When the patient was found to
be tolerant to Azathioprine she was maintained for the next
31 weeks and then subsequently stopped. Patient had slight
nausea and vomiting sensation on medication which was
tolerable. On 6 months follow up, patient is asymptomatic
with no pain or diplopia and maintains visual acuity of 6/6
in the left eye.
3. Discussion
NSOI is a benign non-infectious, inflammatory process
of the orbit, characterised by a polymorphous lymphoid
infiltrate with varying degrees of fibrosis, without a known
local or systemic cause.
The etiopathogenesis of NSOI is unknown. Suggested
theory for NSOI are immune mediated or molecular
mimicry when a foreign antigen has structural similarities
with self-antigen and it may happen after an acute infection.
Treatment options for OAS secondary to NSOI include
corticosteroids and immunosuppressive therapy. Response
to corticosteroids is rapid with dramatic improvement of all
symptoms and signs.
The treatment of THS and inflammatory OAS is often
long with frequent relapses and remissions. Patients tend
to have intolerable side effects due to the long-term steroid
therapy and may benefit with immunosuppressive agents.
In some cases of THS, immunosuppresants like
methotrexate1and azathioprine2–4 and radiation5have been
used.
Smith JR, Rosenbaum JT1have used methotrexate as
treatment modality in a case of THS, it was used at a dose of
25mg per week for a period of 47 months. The patient was
asymptomatic for 19 months, she then experienced recurrent
inflammation which required reinstitution of the drug with
a tapering course of prednisone.
Mazzotta G et al3used azathioprine, 2mg/kg of body
weight in a patient with recurrent THS. She showed
complete remission of the painful ophthalmoplegia within a
few days. Azathioprine was continued for another 6 months,
with no further recurrence of the ophthalmoplegia.
Bhattacharya R et al4reported a case of THS with central
serous retinopathy treated with azathioprine as first modality
of treatment. The patient was given azathioprine 50mg BD.
The patient showed improvement in the condition in 5 days.
Jan Hannerz2studied azathioprine as treatment modality
in 4 patients with THS. They found satisfactory results.
Our case was comparable to the one reported by
Mazzotta G et al.3They reported THS whereas our case
had clinical features of orbital apex syndrome with normal
MRI findings. We had used 1.5 T MRI which might have
missed the early features of cavernous sinus involvement.
212 Arora and Rambhatla / Indian Journal of Pharmacy and Pharmacology 2020;7(3):210–212
The dose of azathioprine used in our case was comparable to
Mazzotta G et al.3Our patient showed complete remission
after 3 weeks. Azathioprine was stopped after 9 months
in our case. We didn’t find any recurrence which was
comparable to Mazzotta et al.3
4. Conclusion
There are multiple causes of OAS. Thorough history,
examination and imaging is required for etiological
diagnosis. NSOI responds well to steroids therapy,
azathioprine can be considered as an option of treatment
in refractory cases and patients who are intolerant or
dependant to steroid therapy.
5. Source of Funding
None.
6. Conflict of Interest
None.
References
1. Smith JR, Rosenbaum JT. A role for methotrexate in the management
of non-infectious orbital inflammatory disease. BrJ Ophthalmol.
2001;85(10):1220–4.
2. Hannerz J. Recurrent Tolosa-Hunt Syndrome. Cephalalgia.
1992;12(1):45–51.
3. Mazzotta G, Alberti A, Sarchielli P, Gallai V. A Case of Tolosa-Hunt
Syndrome Responsive to Azathioprine Treatment. Headache Pain.
2004;15:122–6.
4. Bhattacharya R, Nandy M, Mukherjee K, Chakrabarty P, Polle N. An
observational study of use of azathioprine as immonosuppresant for
the treatment of central serous retinopathy associated with Tolosa Hunt
syndrome. IOSR J Dent Med Sci. 2018;17:66–9.
5. Mormont E, Laloux P, Vauthier J, Ossemann M. Radiotherapy in a Case
of Tolosa–Hunt Syndrome. Cephalalgia. 2000;20(10):931–3.
Author biography
Neha Arora Fellow
Saptagirish Rambhatla Dean and HOD
Cite this article: Arora N, Rambhatla S. Azathioprine in orbital apex
syndrome. Indian J Pharm Pharmacol 2020;7(3):210-212.
... Orbital apex syndrome (OAS) is a complex condition characterized by damage to the oculomotor nerve (CN3), trochlear nerve (CN4), an ophthalmic branch of the trigeminal nerve (CN5), and abducens nerve (CN6) and associated optic nerve (CN2) dysfunction [3,4]. Its etiology encompasses inflammation, infection, neoplasia, vascular abnormalities, trauma, and other factors [3][4][5]. ...
... Orbital apex syndrome (OAS) is a complex condition characterized by damage to the oculomotor nerve (CN3), trochlear nerve (CN4), an ophthalmic branch of the trigeminal nerve (CN5), and abducens nerve (CN6) and associated optic nerve (CN2) dysfunction [3,4]. Its etiology encompasses inflammation, infection, neoplasia, vascular abnormalities, trauma, and other factors [3][4][5]. The orbital apex is a confined space housing critical neurovascular structures, rendering it susceptible to damage, even from minor lesions. ...
... OAS often presents with a combination of symptoms, including vision problems, restricted eye movements, pain, and proptosis. The causes of OAS are varied and can include inflammation, infection, tumors, vascular issues, and trauma [4]. Due to the confined anatomy of the orbital apex, even small lesions can have significant consequences. ...
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Orbital foreign bodies, especially organic materials, can cause severe eye and orbital damage. Orbital apex syndrome (OAS), a complex condition affecting multiple cranial nerves, is often caused by trauma, among other factors. The patient was a three-year-old boy who fell onto a tree stump three days prior. He presented to the emergency department with left-sided eyelid edema, ptosis, traumatic mydriasis, numbness, and ophthalmoplegia and was diagnosed with OAS. Despite treatment with intravenous methylprednisolone, analgesia, and antibiotics, his condition did not improve after the transnasal endoscopic removal of the foreign body. This case highlights OAS caused by a wooden orbital foreign body requiring prompt, multidisciplinary surgical intervention. Early diagnosis and prompt intervention are crucial to preventing devastating outcomes like OAS and permanent visual impairment. Given the limited understanding of this condition, further research is essential to optimize management strategies and improve patient outcomes.
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... In refractory cases, azathioprine, methotrexate, or radiation therapy may be considered for partial response to steroid treatment. 4,10,11 The use of immunotherapy to prevent recurrences is still controversial. Oral azathioprine 50 mg twice daily (2 mg/kg/day) was given with close monitoring of the complete blood count, liver, and renal function tests. ...
... The observational study of azathioprine as an immunosuppressant for central serous retinopathy treatment associated with THS signified that azathioprine could be used as an alternative therapy for THS. 11,12,13 Azathioprine is an immunosuppressive agent and an antimetabolite prodrug. It is an imidazolyl derivative of 6-mercaptopurine in the body that acts by blocking purine metabolism and may impede the synthesis of DNA, RNA, and proteins. ...
... The course of action is appropriate due to a combination of thiopurine analogs into the DNA structure, causing chain termination and cytotoxicity. 11,14,15 The use of azathioprine in our cases has given significant results. Pain intensity measured by NPRS was reduced from moderate to mild (NPRS 4 to 2 in the first case and NPRS 6 to 2 in the second case), followed by complete remission of ophthalmoplegia CONCLUSION Tolosa-Hunt syndrome (THS) presented with unilateral headache and painful ophthalmoplegia. ...
Azathioptrine in Refractory Tolosa-Hunt Syndrome: Two Case Report
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  • Mar 2022
Introduction: Tolosa-Hunt syndrome (THS) is an inflammatory disease with painful ophthalmoplegia and unilateral periorbital headache as detailed by the International Classification of Headache Disorders, 3rd edition (ICHD-3). Azathioprine has been suggested as a second-line treatment in refractory THS when oral corticosteroid only gives a partial response. Case: Two cases of THS, 45-year-old and 41-year-old women with unilateral headache, drooping of the left upper eyelid, and diplopia. They presented with complete ophthalmoplegia and ophthalmic division of trigeminal nerve disturbance. Magnetic resonance imaging (MRI) showed thickening of the left cavernous sinus, suggesting THS, while the other was normal. Corticosteroid (prednisone 1-1,5 mg/day) was given orally for the first two weeks, and according to the Numeric Pain Rating Scale (NPRS), pain intensity was reduced from severe to moderate. As a second-line treatment, azathioprine (2 mg/kg/day) was given afterward, with a significant reduction in pain intensity and remission of ophthalmoplegia within seven days. Azathioprine was used as an immunosuppressive agent and was continued for another three months without any deterioration in neurological deficits. The levels of complement 3, 4 (C3, C4), and C-reactive protein (CRP) were normal in both patients, with a slight increase in erythrocyte sedimentation rate (ESR) and equivocal values on antinuclear antibody (ANA) results. Other differentials of THS were eliminated from history-taking, physical examination, and proper investigations. Conclusion: Azathioprine as a second-line treatment can be used instead of an oral corticosteroid for refractory cases of THS with fewer side effects. Complete remission of ophthalmoplegia and a significant reduction in pain intensity was obtained.
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A role for Methotrexate in the management of non-infectious orbital inflammatory disease
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Full-text available
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To evaluate the clinical usefulness of methotrexate for patients with non-infectious orbital inflammatory disease who fail to respond to systemic corticosteroids and/or orbital irradiation. The medical records of patients with non-infectious orbital inflammatory disease who were treated with methotrexate at Oregon Health Sciences University between June 1993 and June 2000 were examined. Methotrexate was administered at a median maximum dose of 20 mg per week (range 15-25 mg per week) in conjunction with folate supplementation. Patients were followed with regular ophthalmic examinations, as well as serum liver enzyme levels and blood cell counts. Clinical signs of regression of the orbital inflammation, visual acuity, dosage and duration of methotrexate therapy, requirement for concurrent corticosteroid administration, and adverse drug reactions were recorded. The study cohort included 14 patients (24 eyes) with diagnoses including non-specific orbital inflammation (n=7), Tolosa-Hunt syndrome (n=1), thyroid orbitopathy (n=3), Wegener's granulomatosis (n=1), sarcoidosis (n=1), and Erdheim-Chester disease (n=1). In all cases, methotrexate was commenced as a corticosteroid sparing agent. 10 patients (71%) completed a 4 month therapeutic trial of methotrexate. Median duration of treatment for the nine (64%) patients who experienced clinical benefit was 25 months (range 10-47 months). Six responders were ultimately able to cease methotrexate, including the single patient who required concurrent long term corticosteroid therapy. Complications included fatigue, gastrointestinal disturbance, hair thinning and mild, reversible serum liver enzyme elevation. Two patients (14%) discontinued treatment because of adverse effects. Methotrexate is a well tolerated immunosuppressive medication which may benefit patients with recalcitrant non-infectious orbital inflammatory disease.
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A case of Tolosa-Hunt syndrome responsive to azathioprine treatment
Article
  • Sep 2004
OBJECTIVE: Azathioprine has been proposed as a second-line treatment in corticosteroid-insensitive patients affected by Tolosa-Hunt (TH) syndrome. We tested its efficacy in a single patient experiencing recurrent episodes of TH syndrome. HISTORY: The patient was a 28-year-old woman with recurrent episodes of unilateral headache associated with ophthalmoplegia since 1995. Her recurrent episodes were treated with corticosteroids until the end of 2001, when serious side effects prompted us to undertake treatment with azathioprine. RESULTS: Azathioprine, 2 mg/kg of body weight, produced a complete remission of the painful ophthalmoplegia within a few days. Therapy with this agent was continued for another 6 months, with no further recurrence of the ophthalmoplegia. CONCLUSION: Based on this case and on several others in the literature, azathioprine appears to be a safe and effective treatment for TH syndrome and an alternative to corticosteroids.
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Recurrent Tolosa-Hunt Syndrome
Article
  • Mar 1992
Twenty consecutive patients with recurrent Tolosa-Hunt syndrome were studied. One had a parent who suffered from recurrent Tolosa-Hunt syndrome. Thirty-three percent of the patients had also recurrent periods of weeks to months of unilateral periorbital pain without ophthalmoplegia. One patient had cluster headache before the Tolosa-Hunt syndrome started. Some patients had involvement of cranial nerves outside the cavernous sinus region during Tolosa-Hunt syndrome and also between episodes. The same systemic symptoms, i.e. back pain, cold feet, arthralgia, gut problems, varices, vertigo, chronic fatigue, thrombophlebitis, memory deficiency and signs of inflammation in serum, occurred in Tolosa-Hunt syndrome as earlier found in patients with orbital venous vasculitis. Seventy-three percent of the patients had pathologic orbital phlebograms. All patients treated with steroids reacted promptly; four who developed chronic pain syndromes were treated satisfactorily with azathioprine.
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An observational study of use of azathioprine as immonosuppresant for the treatment of central serous retinopathy associated with Tolosa Hunt syndrome
  • Jan 2018
  • 66-69
  • R Bhattacharya
  • M Nandy
  • K Mukherjee
  • P Chakrabarty
  • N Polle
Bhattacharya R, Nandy M, Mukherjee K, Chakrabarty P, Polle N. An observational study of use of azathioprine as immonosuppresant for the treatment of central serous retinopathy associated with Tolosa Hunt syndrome. IOSR J Dent Med Sci. 2018;17:66-9.